Expression pattern and localization of alpha-synuclein in the human enteric nervous system

被引:108
作者
Boettner, Martina [1 ]
Zorenkov, Dimitri [2 ]
Hellwig, Ines [1 ]
Barrenschee, Martina [1 ]
Harde, Jonas [1 ]
Fricke, Tobias [1 ]
Deuschl, Guenther [2 ]
Egberts, Jan-Hendrik [3 ]
Becker, Thomas [3 ]
Fritscher-Ravens, Annette [4 ]
Arlt, Alexander [4 ]
Wedel, Thilo [1 ]
机构
[1] Univ Kiel, Dept Anat, D-24118 Kiel, Germany
[2] Univ Hosp Schleswig Holstein, Dept Neurol, D-24105 Kiel, Germany
[3] Univ Hosp Schleswig Holstein, Dept Gen & Thorac Surg, D-24105 Kiel, Germany
[4] Univ Hosp Schleswig Holstein, Dept Internal Med 1, D-24105 Kiel, Germany
关键词
alpha-synuclein; Enteric nervous system; Neuropathies; Human colon; PARKINSONS-DISEASE; LEWY BODIES; MONOCLONAL-ANTIBODY; COLONIC BIOPSIES; HUMAN BRAIN; PATHOLOGY; DEMENTIA; NEURONS; AGGREGATION; INCLUSIONS;
D O I
10.1016/j.nbd.2012.07.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Alpha-synuclein (alpha-syn) is abundantly expressed in the central nervous system and involved in the regulation of neurotransmission. Insoluble fibrils of phosphorylated a-synuclein (p-alpha-syn) have been implicated in several neurodegenerative diseases (e.g. Parkinson's disease, Alzheimer's disease). The aim of the study was to determine the gene expression pattern and localization of alpha-syn/p-alpha-syn in the human enteric nervous system (ENS). Methods: Human colonic specimens (n = 13, 15-83 years) were processed for alpha-syn and p-alpha-syn immunohistochemistry. Colocalization of alpha-syn was assessed by dual-labeling with pan-neuronal markers (PGP 9.5, HuC/D). For qPCR studies, tissue was obtained from full-thickness sections, tunica muscularis, submucosa, mucosa, and laser-microdissected (LMD) enteric ganglia. Results: Highest alpha-syn levels were detectable within the tunica muscularis and submucosa. Ganglia isolated by LMD showed high expression of alpha-syn mRNA. All myenteric and submucosal ganglia and nerve fibers were immunoreactive for alpha-syn. Dual-labeling revealed colocalization of alpha-syn with both pan-neuronal markers. p-alpha-syn immunoreactivity was consistently observed in specimens from adults with increasing age. Conclusions: alpha-syn is abundantly expressed in all nerve plexus of the human ENS including both neuronal somata and processes. The presence of p-alpha-syn within the ENS is a regular finding in adults with increasing age and may not be regarded as pathological correlate. The data provide a basis to unravel the functions of alpha-syn and to evaluate altered alpha-syn in enteric neuropathies and alpha-synucleinopathies of the CNS with gastrointestinal manifestations. (c) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:474 / 480
页数:7
相关论文
共 28 条
[1]   Mapping of rat brain using the synuclein-1 monoclonal antibody reveals somatodendritic expression of α-synuclein in populations of neurons homologous to those vulnerable to Lewy body formation in human synucleopathies [J].
Andringa, G ;
Du, F ;
Chase, TN ;
Bennett, MC .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2003, 62 (10) :1060-1075
[2]  
Baba M, 1998, AM J PATHOL, V152, P879
[3]   Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis [J].
Basilisco, G ;
Gebbia, C ;
Peracchi, M ;
Velio, P ;
Conte, D ;
Bresolin, N ;
Nobile-Orazio, E .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2005, 17 (04) :449-452
[4]   Multi-organ distribution of phosphorylated α-synuclein histopathology in subjects with Lewy body disorders [J].
Beach, Thomas G. ;
Adler, Charles H. ;
Sue, Lucia I. ;
Vedders, Linda ;
Lue, LihFen ;
White, Charles L., III ;
Akiyama, Haru ;
Caviness, John N. ;
Shill, Holly A. ;
Sabbagh, Marwan N. ;
Walker, Douglas G. .
ACTA NEUROPATHOLOGICA, 2010, 119 (06) :689-702
[5]   α-Synuclein pathology of the spinal and peripheral autonomic nervous system in neurologically unimpaired elderly subjects [J].
Bloch, A ;
Probst, A ;
Bissig, H ;
Adams, H ;
Tolnay, M .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2006, 32 (03) :284-295
[6]   Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine [J].
Boettner, M. ;
Baer, F. ;
von Koschitzky, H. ;
Tafazzoli, K. ;
Roblick, U. J. ;
Bruch, H. -P. ;
Wedel, T. .
NEUROGASTROENTEROLOGY AND MOTILITY, 2010, 22 (02) :168-172+e52
[7]   Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology [J].
Braak, H ;
de Vos, RAI ;
Bohl, J ;
Del Tredici, K .
NEUROSCIENCE LETTERS, 2006, 396 (01) :67-72
[8]   Idiopathic Parkinson's disease:: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen [J].
Braak, H ;
Rüb, U ;
Gai, WP ;
Del Tredici, K .
JOURNAL OF NEURAL TRANSMISSION, 2003, 110 (05) :517-536
[9]   The role of alpha-synuclein in neurotransmission and synaptic plasticity [J].
Cheng, Furong ;
Vivacqua, Giorgio ;
Yu, Shun .
JOURNAL OF CHEMICAL NEUROANATOMY, 2011, 42 (04) :242-248
[10]   The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease [J].
Clayton, DF ;
George, JM .
TRENDS IN NEUROSCIENCES, 1998, 21 (06) :249-254